Millions of people suffer from pain. The pain may be minor, such as headaches, acute lower back pain, and acute muscle pain, or severe, such as chronic pain. Chronic pain may be associated with cancer treatment, HIV, diabetes, or other conditions. Chronic pain can be difficult to treat, with many chronic pain sufferers noting that their pain is not well controlled with current pain medications or that their medications have significant associated adverse effects (for example, nausea and vomiting, dependence, tolerance, etc.).
In an attempt to address the problem of chronic pain management, intrathecal infusion pumps and neurostimulators have been developed. Intrathecal infusion pumps are aimed at continuous, or near continuous delivery of liquid analgesic agents. Many of these infusion pumps are totally implantable, which helps to reduce the risk of infection when compared to the long-term use of external systems. The infusion pump may also be programmable to allow patients or their clinicians to adjust dosing amounts or daily delivery schedule, helping to meet a patient's changing needs.
Neurostimulators are available in various forms and stimulate nerves to relieve pain. Both intrathecal pumps and neurostimulators have drawbacks, including the onset of tolerance, with the treatments becoming less effective over time.
Various approaches for inducing anesthesia or analgesia are known. Systemic delivery of a general anesthetic renders a patient unconscious and unaware of the surgery. In contrast, anesthetics may be applied regionally, for example, to the spine, to the spinal cord (intrathecally or epidurally), or near a nerve in a nerve block to anesthetize only a portion of the patient's body. For general anesthesia, delivery of a general anesthetic to a patient prior to surgery is typically performed using an initial i.v. injection of an induction agent followed by intubation and administration of an inhaled anesthetic gas. It is worthwhile to note that the mechanism of action for general anesthesia is still not completely understood.
Considerable negative side effects may result from administration of general anesthesia. A tube has to be placed into the trachea, necessary to protect against vomiting, which can result in trauma to the upper airway. Many patients report postoperative hoarseness and tenderness of the mouth and throat. In addition, the dose of gases required to reach the targeted neural organs can have an adverse affect on the non-targeted organs, especially the heart, with an increased risk of cardiopulmonary morbidity during general anesthesia. Especially in the elderly, there is substantial evidence for prolonged cognitive dysfunction following general anesthesia (Moller et al., 1988, Lancet., 351:857-861). Additionally, regional anesthetic techniques appear to lead to less overall morbidity and mortality from cardiopulmonary causes as compared to general anesthesia (Rasmussen et al., 2003, Acta Anaesthesiologica Scandinavica, 47:260-266; Rogers et al., 2000, BMJ, 321:1-12).
Certain risks are also associated with inhalation administration of a volatile anesthetic, for example, during general anesthesia. Volatile anesthetic compositions formulated for inhalation generally have relatively low boiling points and high vapor pressures. Older, volatile anesthetic compositions (including ether and cyclopropane) are often flammable or explosive in both their liquid and vapor states, with newer agents much less see (see Williams and Lemke, 2002, Foye's Principles of Medicinal Chemistry, Lippincott Williams & Wilkins, NY). Further, inhalation of vapors by health care personnel in trace amounts have unknown health consequences, and have been the subject of much debate. In the larger amounts used in pediatric operating room's, large amounts of gas can escape during inhalational induction and can cause frank drowsiness or headaches, which is not desirable in an operating room environment. Thus, substantial care must be taken to safely handle volatile anesthetics (including venting of operating rooms) in order to minimize both the risk of inhalation by medical personnel and the risk of fire and care must be taken to try to ensure that there is little or no release of the volatile anesthetic into the atmosphere at all stages of handling.
Clearly, there exists a need for improved methods for pain management and local and regional anesthesia. Further, there exists a need for volatile anesthetic compositions that have reduced risks, as described above, associated with their use. There is also a need for methods for delivering such improved volatile anesthetic compositions for treating pain without substantially interfering with motor function. The current invention fulfills these needs.